Several cells have been described in lymphoid tissue which have long dendritic processes and are morphologically distinguishable from lymphocytes and typical macrophages. One such dendritic-type cell has been described in lymphoid follicles. This cell has the ability to bind and retain antigen for long periods of time (eg, T 1/2 of HSA on mouse dendritic cells is approximately 2 months). To distinguish this cell from other dendritic-type cells in lymphoid tissue, including Langerhans cells and the adherent dendritic cells described by Steinman and Cohn, we will refer to this cell in this proposal as the "follicular antigen-binding dendritic cell" or FAD-cell". Although this cell does not appear to play a major role in the initiation of the immune response, the FAD-cell appears to play a major role in the maintenance and regulation of the immune response. Our data indicate that circulating antibody levels are maintained and regulated in vivo by persisting antigen in conjunction with an antibody feedback system. The antigen persisting in the lymphatics after the first few weeks is bound to the surface of FAD-cells. The feedback system appears to prevent the FAD-cell associated persisting antigen from inducing antibody synthesis when circulating levels are high. However, when antibody levels fall, the antigen is exposed and stimulates memory cells to synthesize antibody and to produce additional memory cells. We propose that the level of both circulating antibody and 8-cell memory could be maintained by this mechanism. The data to be obtained from the proposed research should provide a basis for critically evaluating this mechanism for maintaining circulating antibody levels and immunological memory.